Regulation of translation

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  • Regulation of translation
    • can be global or mRNA specific
      • mRNA specific
        • means of controlling gene expression in cells where transcription is repressed or absent
        • means of producing the right amount of the right proteins at the right time
      • global
        • eIF4E-bp
          • stimulated by environmental factors, such as stress, viral infection, starvation and heat shock
          • eIF2 is phosphorylated at its alpha subunit during viral infection
            • results in generalised global translational repression
          • global upredulation does occur
            • phosphorylation of the eIF4E-binding protein
              • normally sequesters eIF4E but here causes it to be released so it can interact with eIF4G and form the translation machinery
    • The ferritin gene
      • regulation by RNA-binding proteins as opposed to translation initiation factors
      • control of iron levels in cells
        • normally tightly regulated as iron plays role in active site of many enzymes
        • excess iron can oxidise cellular compartments
          • when iron level high therefore necessary to prevent toxic levels accumulating
        • iron levels low - available free iron needs to be released in order for iro-dependent enzymes to operate
      • ferritin sequesters iron in cells
        • 5'UTR of ferritin mRNA contains iron response elements - hairpin stem-loop structures
          • act as binding sites for the iron response-building proteins
            • IRP1
            • IRP2
            • in absence of iron IRP1 and IRP2 bind the iron response elements very well, preventinf the small ribosomal subunit from scanning the ferritin mRNA for the AUG start codon
            • in presence of iron, IRP1 and IRP2 are rendered inactive and cannot bind the response element, so ferritin mRNA can be translated
              • ferritin protein produced which sequesters iron and prevents toxic levels
      • transferrin receptor
        • binds to the transferring protein that carries iron around the blood
        • encoded by the TfR gene
        • able to import transferrin that is complexed to iron into a cell
        • iron response elements also present (at the 3'UTR of the TfR mRNA this time
          • presence of iron
            • iron response elements not occupied by IRPs
              • TfR mRNA unstable and degraded
                • less protein made - therefore less iron transported into cells
          • absence of iron
            • IRPs bound to iron response elements on TfR mRNA
              • TfR mRNA protected from degradation and stable
                • more TfR protein made - more iron transported into cells to be used in active site of enzymes
    • regulation by miRNAs
      • non-coding RNAs
      • regulate target genes at the level of translation
      • lin-4 miRNA
        • in C.elegans
        • binds to 3'UTR of lin-14 and lin-28 mRNAs
          • genes expressed in developmental timing
          • results in translational repression - normal event in normal development
    • developmental coregulation proteins
      • A-P system in Drosophila is established by BICOID morphogen gradient
        • bicoid protein is organiser of anterior development
        • gradient involves several morphogens e.g. hunchback, caudal and nanos
        • bicoid mRNA translated mainly at the anterior end of an oocyte
          • then inhibits translation of caudal mRNA at the anterior end
        • at posterior end, nanos protein inhibits translation of hunchback mRNA
          • no hunchback protein at the posterior end


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